Genetic changes increase the likelihood of fatty liver disease
When they hear the term fatty liver, many people immediately think of patients who consume too much alcohol and/or eat too much unhealthy food or are overweight. But even people who are not overweight and who eat a healthy diet can develop fatty liver disease. Researchers have now gained new insights into this.
According to a recent Message from the Max Planck Institute of Molecular Cell Biology and Genetics, a new study has identified two genes previously known to cause cancer as regulators of metabolism in the liver. Changes in these genes therefore influence the probability of developing a disease fatty liver to get sick. The study results have now been published in the journal “Nature Communications” released.
Facilitate identification of persons at risk
The worldwide epidemic of obesity (obesity) has increased the risk of fat accumulating in the liver, which is a precursor to liver inflammation and liver disease. A still perplexing paradox, however, is the development of fatty liver in lean and normal-weight individuals and in people who eat a healthy diet.
It is known that two genes, RNF43 and ZNRF3, are mutated in liver cancer patients. However, their role in the development of liver cancer was previously unknown. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden now report that a loss or mutation of these genes in non-obese mice fed a normal diet leads to accumulation of lipids and inflammation in the liver leads.
According to the information, these genetic changes not only lead to an increased accumulation of fat, but also to an increase in liver cells (hepatocytes). In humans, these changes also increase the risk of developing nonalcoholic steatohepatitis (NASH, inflamed liver) and fatty liver, and shorten the life expectancy of those affected.
The knowledge that has now been gained could make it easier to identify people at risk and enable new therapeutic measures and better treatment of the disease.
Causes and mechanisms of liver disease
The liver is our central metabolic organ, essential for detoxification and digestion. Chronic liver diseases such as cirrhosis, non-alcoholic fatty liver disease (NAFLD) and NASH, and liver cancer are on the rise worldwide, killing two million people each year.
Therefore, it is more important than ever to understand the causes and the underlying molecular mechanisms of liver diseases in order to prevent, control and treat the growing number of cases.
Previous genomic cancer studies identified RNF43 and ZNRF3 as genes that are mutated in patients with colorectal and liver cancer. However, their involvement in liver disease has not been explored.
Meritxell Huch’s research group at the MPI-CBG, together with colleagues at the Gurdon Institute (Cambridge, UK) and the University of Cambridge, has now investigated the mechanisms by which changes in these two genes can influence the development of liver diseases.
chances of survival examined
In order to get to the bottom of this question, the scientists worked with mice as an animal model, with data from patients, with human tissue and with so-called liver organoid cultures, which are three-dimensional cellular microstructures made from hepatocytes, those of the liver in a bowl resemble
“Using the organoid, we were able to grow hepatocytes that were only mutated in these genes, and we saw that the loss of these genes triggers a signal that regulates lipid metabolism,” explains Germán Belenguer, first author of the study and postdoc in Meritxell’s group whoops
“As a result, the lipid metabolism is no longer under control and lipids build up in the liver, which in turn leads to fatty liver. In addition, the activated signal causes the hepatocytes to multiply uncontrollably. Both mechanisms together promote the progression of fatty liver disease and cancer.”
The researchers then compared the results from the experiments with patient data in a publicly available dataset from the International Cancer Genome Consortium. They examined the chances of survival when the two genes are mutated in liver cancer patients and found that patients with these mutated genes have fatty liver disease and a poorer prognosis than liver cancer patients in whom the two genes are not mutated.
“Our results can help to identify people with an RNF43/ZNRF3 mutation who have an increased risk of developing fatty liver or liver cancer,” says Meritxell Huch. “With the alarming increase in fat and sugar consumption worldwide, it could be important for therapeutic measures and management of the disease to identify those individuals who are predisposed to it because of their genetic mutations, especially at very early stages or even before the onset of the disease ‘ she adds.
“We will need further studies to further characterize the role of the two genes in human fatty liver disease, NASH, and human liver cancer, and to identify therapeutics that could help those patients who are inherently predisposed to develop the disease.” to develop.” (ad)
Author and source information
This text corresponds to the requirements of medical specialist literature, medical guidelines and current studies and has been checked by medical professionals.
Sources:
- Max Planck Institute for Molecular Cell Biology and Genetics: Development of fatty liver disease with a healthy diet, (accessed: January 17, 2022), Max Planck Institute for Molecular Cell Biology and Genetics
- German Belenguer, Gianmarco Mastrogiovanni, Clare Pacini, Zoe Hall, Anna M. Dowbaj, Robert Arnes-Benito, Aleksandra Sljukic, Nicole Prior, Sofia Kakava, Charles R Bradshaw, Susan Davies, Michele Vacca, Kourosh Saeb-Parsy, Bon-Kyoung Koo, Meritxell Huch: RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state; in: Nature Communications, (veröffentlicht: 17.01.2022), Nature Communications
Important NOTE:
This article contains general advice only and should not be used for self-diagnosis or treatment. He can not substitute a visit at the doctor.
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